Rheumatoid synovial effusions (and other inflammatory joint fluids are characterized by large numbers of T cells, many of which are activated, and another ill-defined population lacking cell surface receptors (E negative, Ig negative, Fc negative). Little is known about the functional significance of either population. There is evidence, however, for natural killer cell activity mediated by an Fc receptor negative NK cell. These characteristics are reminiscent of the results of the in vitro autologous mixed leukocyte reaction. We propose to analyze the following hypothesis; namely, in the rheumatoid joint B lymphocytes, transformed by an undefined stimulus, generate an autologous MLR. This leads to activation of T cells and the elaboration of factors that augment nonspecific cytotoxic activity. An additional consequence of this reaction would be the generation of large amounts of nonspecific T cell-derived helper activity. This thesis would predict that in the rheumatoid joint one would find evidence of an increased or secondary type of autologous MLR, an unusual population of AMLR stimulator cells, the presence of nonspecific cytotoxic cells lacking Fc receptors, and perhaps specific cytotoxic cells recognizing lymphocyte membrane defined antigen induced by the B cell transforming agent.